The broad objectives of this study are to delineate the biological role of complex carbohydrates (glycosphingolipids, glycoproteins and glycosaminoglycans) in the different cell types found in nervous tissue and thereby understand and eventually prevent certain types of neurologic dysfunction in children. One approach will be to characterize the factors which normally regulate the synthesis of marker glycosphingolipids (such as sulfatide in Schwann cells and gangliosides in neurons) in mouse neurotumor cell lines. We will test the effect of both protein and steroid hormones, cyclic nucleotides, prostaglandins, and neurotransmitters, as well as some metabolic toxins and heavy metal toxins thought to cause dysmyelinating diseases. A second study will investigate the interaction between neuroblastoma, astrocytoma and Schwannoma cells in culture and the regulation of expression of differentiated characteristics, in single and hybridized cell cultures. A third study will attempt to evaluate the role of lipoproteins in cell-cell interaction, using purified serum lipoprotein and human cultured skin fibroblasts from patients with inborn errors of lipid metabolism as an initial model system, and later extending the study to mouse neurotumor cell lines. A fourth study will continue our studies on inborn errors of glycoprotein metabolism in an attempt to elucidate the role of L-fucose and alpha-L-fucosidase in nervous system development and the potential for eventual enzyme replacement therapy of an inherited lysosomal storage disease.